Arenavirus infections range in character from persistent and inapparent in certain species of rodent hosts to severe acute disease in incidental hosts such as man. Because of this dual capability, arenaviruses have provided productive and important models for the study of acute and persistent virus infections. I have previously described the polypeptide structure of LCM virus. The overall goals of this project are to relate the biochemistry of arenavirus structure and replication to the immunobiology of acute and persistent infections. For these studies, monoclonal antibodies made in vitro and specific for defined determinants on the LCM virus polypeptides will be used as probes to define the expression of and quantitate viral antigens during infection, and to define the viral antigens expressed at the cell surface which are important in T-cell mediated immune recognition. Arenaviruses are important human pathogens particularly in the Western hemisphere and Africa. Antigenic cross reactivity and cross protection in vivo have been reported for these viruses. I will investigate the basis for this cross reactivity using monoclonal antibodies to define the cross reactive antigens and tryptic peptide mapping to analyse the relationships at the molecular level among these viruses. Cross reactivity at the level of the cytotoxic T-cell will be assessed in order to determine whether T-cell cross reactivity plays a role in cross protection. These studies will provide basic information necessary both to interpret the evolution of the arenaviruses and to plan rational strategies toward development of antiviral vaccines against the human pathogens of the arenavirus group.